Implantable drug delivery device

ABSTRACT

The implantable drug delivery device comprises at least an implantable pump, a reservoir and a delivery chamber.

This application is the U.S. national phase of International ApplicationNo. PCT/IB2006/052864, filed 18 Aug. 2006, which designated the U.S.,the entire contents of which is hereby incorporated by reference.

TECHNICAL FIELD

The present invention generally relates to an implantable device.

More specifically, the present invention relates to a high-precisionimplantable drug delivery device with reservoir means.

BACKGROUND OF THE INVENTION

Peripheral vascular disease (PVD) results from the development ofatherosclerosis, which in the lower limbs leads to poor circulation andpoor perfusion of leg tissues, a condition called critical limb ischemia(CLI). In severe forms CLI manifests itself with leg pain, inability towalk, ischemic ulcers in the feet and toes, arterial emboli, and, atadvanced stage, gangrene. Risk factors include smoking, diabetes,obesity, high blood cholesterol, a diet high in fats, and having apersonal or family history of heart disease. In the United States theprevalence of peripheral vascular disease is 3%, with the prevalence ofdiabetes-induced PVD rising to 2.8%. About 82,000 non-traumaticlower-limb amputations are performed each year among people withdiabetes. Clearly, solutions improving the conditions and treatmentsoptions for CLI are in need, especially in view of the ever increasingincidents of diabetes-related PVD.

The progression of PVD may be stopped if sufficient blood flow runsthrough the diseased vessels. Increase in blood flow can be achievedthrough exercise, which has been shown to be beneficiary to the outcomeof disease. Alternatively, blood flow may be increased by continuous orperiodical administration of drugs into the blood stream certain drugsthat will act either locally or at the distal bed. This can be achievedby the intra-arterial release of angiogenetic or vasodilatatorysubstances.

Implantable medical devices suitable for the delivery of drug are knownper se in the art. Swiss patent N^(o) 688 224 discloses an implantabledevice for the delivery of liquid pharmaceutical drugs in the humanbody. Other examples of similar devices are disclosed in US2004/0249365, WO 02/08233, WO 02/083207, DE 4123091, WO 03/089034, GB2174218 and WO 96/41080, all incorporated by reference in the presentapplication.

In the above-mentioned Swiss patent N^(o) 688 224, the disclosed devicecomprises an axial piston pump. The piston is driven under control inrotation and axial translation. A fluid reservoir is connected to asuction side of the pump. The pump preferably has a ceramic cylinder andpiston. A refilling connection for the reservoir is re-sealable. Theintegral rotary drive has a separate control unit. Pump, reservoir anddrive are coaxial in a cylindrical casing. Alternatively the drive isexternal, a non-contact coupling transmitting rotary motion to thepiston. The end face of the cylinder has a cam profile. An eccentric camfollower peg, which produces the axial motion, is attached to thepiston. This system is rather complicated as it involves at least twodisplacements of the piston, i.e. a rotation coupled to a translation.According to this geometry, it is necessary to use specific means totransform the rotation created by the motor into a translation. Thedisclosed means complicate the construction, are a dysfunction risk andconsume energy.

Another prior art pump is known from US patent application 2004/0044332.This publication discloses an implantable device for deliveringmedicines in liquid form comprising: a reservoir provided with an inletand an outlet, said reservoir being adapted to expel the liquid; avariable volume chamber provided with an inlet and an outlet, the volumeof the variable volume chamber being in particular smaller than that ofthe reservoir; a first conduit communicating the outlet of the reservoirwith the inlet of the variable volume chamber to fill the latter; asecond conduit whereof one of the ends is connected on the outlet of thevariable volume chamber.

In this prior art, in fact two variable volume chambers are used (onebeing the reservoir), separated by a valve, and function by using theirrespective restoring forces to expel a desired quantity of liquid (forexample medicine).

SUMMARY OF THE INVENTION

Accordingly, it is an aim of the invention to improve the known devicesand methods.

It is also an aim of the present invention to provide a simpleimplantable device that is reliable.

Another aim of the present invention is to provide a system that allowsa better dosage of the expelled liquid.

A further aim of the invention is to provide a system of small sizeallowing small animal research and laparoscopic implantation.

It is also an aim of the present invention to provide a reservoirsuitable for use with the present pump.

These aims are achieved thanks to the apparatus defined in the claims.

The result is a promising solution, in which the idea is to infuse thespecific drugs directly into an artery, the intrathecal space,intracranially or any other body location using a high-precision,telemetrically controlled, implantable intra-arterial drug infusiondevice. A high-concentration drug is stored within the implant and thedosing is low so that drug delivery can take place over long periods(weeks to months or years). Alternative designs may incorporate accessports for transcutaneous drug refill. Because the drugs are administeredlocally with non-systemic effects, the technology probes for auser-defined, low-dosage, high-precision and high efficiency drugdelivery system.

Other advantages of the present invention include:

-   -   1. Small compact size to facilitate peripheral implantation,        intracranial implantation, cardiac applications, laparoscopic        insertion and small animal research.    -   2. High-precision bolus administration    -   3. Dosing independent of load (i.e., arterial pressure or        intracranial pressure at distal end of delivery catheter)    -   4. Externally programmable/activated for continuous, periodic or        user-defined drug administration    -   5. MRI safe and compatible.

Advantageous embodiments of the invention are the subject-matter of thedependent claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Other features and advantages of the present invention will appear moreclearly from reading the following detailed description of embodimentsof the invention which are presented solely by way of non-restrictiveexamples and illustrated by the attached drawings in which:

FIGS. 1A to 1H show detailed cut views of the invention according to afirst embodiment;

FIG. 2A to 2H show detailed cut views of the invention according to asecond embodiment; and

FIGS. 3 to 7 show detailed views of the invention according to a thirdembodiment.

FIG. 8 shows a general cut view of a pump according to the presentinvention.

FIGS. 9A to 9C illustrate an example of a release chamber suitable foruse in the system according to the present invention.

FIGS. 10A to 10D illustrate an example of a reservoir suitable for usein the system according to the present invention.

FIGS. 11A to 11D show a specific embodiment of an eccentric axis.

DETAILED EMBODIMENTS OF THE INVENTION

FIG. 1A shows a transverse cut view of a first embodiment of the pumpaccording to the invention.

The pump comprises an external body 1 with an inlet 2 and an outlet 3.Said inlet 2 and said outlet 3 are connected, in a known fashion forexample as disclosed in US 2004/0044332 to conduits or catheters inorder to transfer liquid (for example a drug) from a reservoir to thesite to be treated. These conduits are not represented in FIG. 1 for thesake of simplicity but are similar to the conduits disclosed in the USpublication mentioned above. A more detailed description of examples ofsuch catheters is given with reference to FIGS. 9A, to 9C and 10A to 10Din the present application.

Inside the body 1, there is a cylinder 4 rotating around a cylinder axis5. Inside the cylinder 4, there is further a piston 6 which is driven inrotation by the cylinder 4 and which is rotated around a piston axis 7.The axis 7 is eccentric with respect to the axis 5 thus causing thepiston 6 to move laterally inside the cylinder 4 when said cylinder isrotating.

In the body 1, the inlet 2 ends into an inlet chamber 8, which has avariable volume. This chamber 8, in this embodiment, is defined mainlyby the relative position of the piston 6 in the cylinder 4 and insidewall of the body 1.

The system comprises in addition first and second temporary chambers 9and 10 the use of which will be explained further below.

Finally, to maintain the sealing, the piston 6 carries two seals 11 and12, for example O-rings.

In FIG. 1B, the system is shown with the cylinder 4 and piston 6 rotatedfrom about 30° clockwise relatively to the external body 1. In thisposition, the chamber 8 is now closed, i.e. is not linked anymore withinlet 2, and the volume 8 is defined by the end B of the piston 6, theinner walls 13, 14 of the cylinder 4 and the inner wall 15 of theexternal body 1.

In FIG. 1C, the cylinder 4 and piston 6 are further rotated from about90° clockwise (value taken from the position of FIG. 1A) relatively tothe external body 1. In this position, due to the fact that cylinder 4and piston 6 rotate around axes which are eccentric with respect to eachother, the piston 6 moves laterally with respect to the cylinder 4 thusreducing the volume of the chamber 8. At the same time, once cylinderand piston have left the position illustrated in FIG. 1B, the chamber 8is linked to the temporary chamber 9 and by way of consequence to outlet3. Accordingly, the liquid present in the chamber 8 is expelled throughoutlet 3 by the relative motion of the piston 6 in the cylinder 4.

At the same time, as can be seen on the right hand side of FIG. 1C, aninlet chamber 8′ has been created on the side A of the piston 6 by itslateral movement relatively to the cylinder 4, this chamber 8′ beingconnected to the second temporary chamber 10 and to inlet 2.

Further rotation of the cylinder 4 and piston 6 relatively to theexternal body 1 as illustrated in FIG. 1D shows that chamber 8 isfinally totally suppressed be the displacement of piston 6 but at thesame time the displacement creates another chamber 8′ at the end A ofthe piston 6, the displacement of the piston 4 to form chamber 8′creating at the same time a suction force to fill chamber 8′.

After a rotation of 180° clockwise of piston 6 and cylinder 4 from theposition represented in FIG. 1A, the system is in the positionrepresented in FIG. 1E, with the ends A and B of the piston 6 ininverted positions.

FIG. 1F to 1H show exactly the same movement of the system asrepresented in FIGS. 1A to 1D and the explanations given above applycorrespondingly. Finally after the situation represented in FIG. 1H,further clockwise rotation of the piston 6 and cylinder 4 ends in theposition represented in FIG. 1A and the cycle starts again.

As can be readily understood from the above description, the systemallows to form a variable volume chamber (8 or 8′) by the use of apiston and an eccentric system which transforms a pure rotation motioninto a combination of rotation and lateral relative displacement.

FIGS. 2A to 2H show a second embodiment of the system of body, cylinderand piston. In this case, no eccentric axes (as the axis 5 and 7 of thefirst embodiment) are used but the system uses a pressure differential.More precisely, it uses the principle according to which the pressure ofthe liquid (for example a drug) is higher at the inlet than at theoutlet.

As shown in FIG. 2A, the liquid enters into a chamber 22 through inlet17 in the body 16 and pushes the cylinder 21 upwards in therepresentation of FIG. 2A since the pressure at the inlet side 17 ishigher than the pressure at the outlet 18 side. The liquid also fillsthe temporary chamber 23 and seals 25 and 26, for example O-rings, areprovided on the piston 21.

In FIG. 2B, the cylinder 19 and the piston 21 are rotated clockwisearound axis 20 in the body 16 of an angle of about 30° and the chamber22 is now closed, delimited by the end B of the piston 21, the innerwalls 27 and 28 of the cylinder and inner wall 29 of the body 16.

A further clockwise rotation of the cylinder 19 and the piston 21 ofabout 90° (value taken from the position of FIG. 2A) brings the systemin the position represented in FIG. 2C. As can be understood whenconsidering FIGS. 2B and 2C, clockwise rotation of the cylinder 19 andpiston 21 from the position of FIG. 2B allows the temporary chamber 24connected to inlet 17 to be connected to the end A of the piston 21,thus allowing the liquid under pressure in the inlet 17 to applypressure against the 21 piston at its end A. Since the pressure at theinlet 17 is higher than the pressure at the outlet 18, the piston willmove laterally in the direction of end B and the volume of the chamber22 is diminished thus evacuating the liquid present through the outlet18 and at the same time a chamber 22′ is formed at the end A of thepiston 21. This situation is represented in FIG. 2C.

A further clockwise rotation of the cylinder 19 and the piston 21 ofabout 90° ends in the positioning represented in FIG. 2D, repeated inFIG. 2E which shows the same position of the elements.

Then, a new cycle may start as represented in FIGS. 2F to 2H, which isin fact similar to the cycle represented in FIGS. 2C to 2D and thedescription made above applies correspondingly. The only differenceconcerns the ends A and B of the piston, which are inverted.

The final position represented in FIG. 2H is identical to the positionrepresented in FIG. 2A, the cylinder 19 having made a rotation of 360°as represented successively in the FIGS. 2A to 2H.

FIGS. 3 to 7 show another embodiment of the invention in which thetemporary chambers are placed differently with respect to the first twoembodiments.

In FIGS. 3 and 4, a first perspective exploded view of this thirdembodiment is represented. This embodiment comprises a cage 30, acylinder 31, a piston 32, and a first disc 33. The cylinder 31 inaddition comprises a chamber 34 receiving the piston 32, two channels35, 36 and an opening 37. The piston 32 also comprises an opening 38 andpreferably two seals 39 such as O-rings.

The disc 33 further comprises two banana-shaped chambers 40, 41 on theside of the disc 33 opposite the piston and two openings 42, 43 whichopen on the piston side of the disc 33 and end inside the banana-shapedchambers 40, 41. Finally, the disc 33 also comprises a central opening44.

Cage 30, cylinder 31 and disc 33 are attached together to form a firstassembly, with the disc 33 and the cylinder relatively placed such thatthe openings 42, 43 of the disc are aligned with the channels 35,respectively 36 of the cylinder 31, and this assembly is rotated by amotor (not shown), the piston 32 moving perpendicularly to the axis ofrotation of the assembly.

In a variant, it can be envisaged to form cylinder 31 and disc 33 in onesingle part rather than two separate parts, one criterion for choosing aconstruction in single part or in two separated parts may be thematerial used for the disc and for the piston.

The pump also comprises a second assembly including a body 45 with aninlet 46 and an outlet 47 and carries a second disc 48. The second disc48 comprises two openings 49, 50 which are connected to inlet 46,respectively outlet 47, and a first axis 51 which, when both assembliesare mounted together extends though the opening 44 of the disc 33 andthe opening 37 of the cylinder 31. There is also a second axis 52,eccentrically disposed with respect to first axis 51, which extendsthough the opening 38 of the piston 32 when both assemblies are mountedtogether. This state is represented in FIGS. 5 to 7, FIG. 6 showing acut view of the assembly along axis A-A of FIG. 5, whereas FIG. 7illustrates a front view along axis B-B of FIG. 5, in which the sameelements are identified by the same numerical references.

The system functions in the following manner. When the piston 32 is atfull stroke, the openings 49 and 50 of disc 48 are between the twobanana-shaped chambers 40 and 41 and there is no transfer of liquid.When the first assembly comprising cage 30, cylinder 31, piston 32 anddisc 33 starts rotating relatively to second assembly comprising body45, disc 48 with axis 51 and 52, the fact that the axis 51 and 52 areeccentric displaces the piston 32 laterally (for example downwards inFIG. 6) which consequently reduces the volume of the chamber 53. At thesame time that the piston 32 moves, the openings 49 and 50 are connectedto the banana-shaped chambers 40, 41 allowing liquid present in thechamber 53 to be transferred in a banana-shaped chamber 40 or 41 throughchannels 35 or 36. For the sake of clarity, let's assume it isbanana-shaped chamber 40 that is filled by the liquid expelled fromchamber 53 by the displacement of piston 32. This is thus done throughchannel 35 and opening 43. However, since the banana-shaped chamber isalso connected to opening 50, the corresponding volume of liquid whichis transferred from chamber 53 into banana-shaped chamber 40 by thedisplacement of the piston 32 is expelled through opening 50 and outlet47.

At the same time, at the other end of the piston, an inverse behaviourtakes place. While the volume of the chamber 53 (see FIG. 6) at one endof the piston 32 is reduced by the displacement of the piston 32, achamber is formed at the other end of the piston 32 by its motion (seethe principles exposed in relation to the embodiments of FIGS. 1A-1H and2A-2H). This chamber is connected via channel 36 to the otherbanana-shaped chamber 41 through opening 42. Hence displacement of thepiston to form a chamber will “aspirate” liquid present in banana-shapedchamber 41 and since this chamber is further connected to inlet 46through opening 49, the banana-shaped chamber 41 will be filled by acorresponding volume of liquid taken from a reservoir.

As can be readily understood from the description above, each rotationof 180° will allow the system to expel a volume of liquid correspondingto the volume of the chamber 53 (see FIG. 6) and at the same time tofill a chamber with the same volume of liquid. It can also be easilyunderstood that the volume of expelled fluid can be a function of thedegree of rotation and through selectively stopping the rotation ofpiston 6 at intermediate positions during rotation. In this manner onemay deliver volumes of fluid which are known fractions of the strokevolume expelled during a 180° rotation.

Interesting in this third embodiment is the use of discs, which, byrelative rotation, allow the opening and the closing of the circuit. Inaddition, such discs have a large contact surface, which improves theleakproofness of the system.

The present invention can also be used to deliver drugs to otherorgans/tissues. One application is pain relieve drugs in the spine. Astraightforward use might be in the delivery of intra-arterialchemotherapy in different malignancies. This approach seems particularlyeffective for liver (hepatocellular and metastatic colorectal) tumours,but also for uterine, gastric, head and neck and intracerebralmalignancy. Drugs that could be administered by the present invention inthis context might include cisplatin and fluorouracil. Otherapplications might include administration of vasodilators such aspapaverine for recurrent cerebral vasospasm and the long-termadministration of anti-fungal agents for particularly resistantinfections.

As can be readily understood from the above description, the systemaccording to the invention is rather simple. In addition, it isvalveless which is a clear advantage over the known systems. There isalso no fluidic communication between inlet and outlet so that even ifthe system is blocked, there is no risk that the reservoir emptiesitself in the body carrying the system.

Typically, the device can be made in plastic or metal (for examplestainless steel) or a combination of both. The discs can be made ofplastic, metal, silicon or ceramics. In a variant, as mentioned above,the disc 33 could be made integral with the cylinder 31.

FIG. 8 shows in a schematical way a cut side view of a complete pumpaccording to the third embodiment of the invention corresponding toFIGS. 3 to 7. The represented pump comprises an outer body 55 withbatteries 56, an electronic circuit 57, a motor 58, the cage 30, the twodisks 33 and 48, the inlet 46, the outlet 47 and the axis 51, asdescribed with reference to FIGS. 3 to 7. Around the inlet 46, there isin addition a reservoir 59 in which the liquid to be delivered ismaintained and the liquid can be introduced in said inlet 46 throughopening 60. The representation of FIG. 8 is a schematical representationcomprising the third embodiment disclosed above and the description ofthis embodiment with FIGS. 4 to 7 applies correspondingly. As said, thisis only an example and the principles of the first and secondembodiments can also be used in the assembled pump of FIG. 8 withcorresponding modifications and adaptations.

Also, FIG. 8 represents a preferred embodiment in which the entireimplantable system is embedded in the same body 55, including motor 58,energy source 56, electronic circuit 57 and reservoir 59. Of course itcan be envisaged for different reasons (especially to reduce the size ofthe body 55) not to include all these elements in the same body. Oneelement that could be removed is the energy source 56, when batteriesare used: indeed batteries must be changed after a certain time and thisoperation would imply the removal of the implanted device. To overcomethis specific problem, an external source may be used to transmit energytelemetrically or through other suitable means to the motor 58 and thecircuit 57. Other variants are given at the end of the presentdescription.

A non-limiting example of a delivery chamber that can be used in thepresent system is described with reference to FIGS. 9A to 9C.

A main feature of this delivery chamber is that it is elasticallycompliant therefore the pump fills the elastic chamber at each strokewith liquid. The elastic chamber recoil then brings the chamber back toits original volume and, by doing so, empties gradually the liquid at anoutlet end of the chamber. The advantage of using such a chamber is thefact that the liquid is not delivered in one single stroke into the bodycarrying the system but rather is delivered slowly (depending on thecharacteristics of the chamber) over time.

Accordingly, the elastic delivery chamber 70 (FIG. 9A) comprises aninlet 71 connected to the pump (not shown in FIG. 9A) for examplethrough the outlet 3 of FIGS. 1A to 1H, or 18 of FIGS. 2A to 2H, or 47of FIGS. 3 to 6 and 8 and an outlet 71 in the shape of a catheter forthe delivery of the liquid pumped into the chamber 70. By itscompliancy, the chamber 70, when regaining its original volume, expelsthe liquid through outlet 72/catheter.

FIGS. 9B and 9C illustrate two exemplary ways of realizing the end ofthe catheter 72 with a backstop. In FIG. 9B, the backstop has the shapeof a back flow stop valve 73 and in FIG. 9C a deformation 74 of the endof the catheter 72 is used to the same effect. These configurations keepthe end of the catheter 72 closed, unless a positive pressure gradientcreated by the movement of piston 6 (see FIGS. 1A to 1H) or piston 21(see FIGS. 2A to 2H) or piston 32 (see FIGS. 3 to 6) forces the catheterend to open so that the fluid is expelled. The closed catheter endserves in blocking cells, body fluids or tissues from entering thecatheter, thereby provoking a clogging up of the conduit. Of course,other equivalent means can be envisaged for the same purpose.

In FIGS. 10A to 10D, several non-limiting examples of a liquid reservoirsuitable for use in the present invention are disclosed. In particular,a feature that is sought for such reservoirs is a small size (especiallywhen empty) to allow their insertion in a body through a trocar orsimilar device.

A first embodiment is illustrated in FIG. 10A, which shows a reservoir80, with a septum 81 used to fill the reservoir from the outside, in aknown fashion. A pump 82 (corresponding to the pump described above) isintegrated in the reservoir 80. Further elements integrated in thereservoir are an electrical source 83 (for example batteries), anelectronic device 84 used to control the system and an antenna 85 thatis used for receiving instructions from outside, for example from awireless emitter used by a doctor. This allows, for example a distanceprogramming of the electronic device. An outlet catheter 86 is connectedto the pump, for example corresponding to the inlet catheter 71 of FIGS.9A to 9C to fill a delivery chamber as disclosed in these figures.

A second embodiment is represented in FIG. 10B. In this embodiment, thereservoir 87 still comprises a septum as the reservoir of FIG. 10A butthe pump 88 with electrical source and electronic control means are notintegrated in the reservoir 87. Rather, the pump 88 is connected to thereservoir via a feed catheter 89. On the outlet side of the pump 88, anoutlet catheter 86 is connected, said outlet catheter corresponding, forexample, to the inlet catheter 71 represented in FIGS. 9A to 9C to filla delivery chamber as disclosed in these figures.

A third embodiment of a reservoir is illustrated in FIG. 10C. In thisembodiment, the reservoir 90 has an elongated shape, so that it can beinserted in the human body through trocars. Part or the entire reservoir90 is made of an inflatable material. Fluid or drug can be deliveredinto the reservoir via an access port 91, said access port carrying theseptum 92 for the filling of the reservoir, such as those foundcommercially for cancer treatment or in adjustable gastric rings. Saidliquid is introduced into the reservoir by transcutaneous injection intothe port 91, said port been connected to the reservoir via a flexiblefeed catheter 93. When said liquid is introduced in the reservoir 90,said reservoir expands to accommodate the desired volume of liquid. Thisembodiment also uses a feed catheter 89 from the reservoir to the pump88 and an outlet catheter 86, as in the preceding embodiments. Inanother form of execution, the access port 91 with its septum 92 areintegrated into the inflatable reservoir 90, eliminating the need forthe feed catheter 93.

In a variant, the reservoir 59 represented in FIG. 8 has the samefeatures of expandability of the reservoir 90 of FIG. 10C. In thisvariant, the need for feed catheter 89 as represented between thereservoir 90 and the pump 88 in FIG. 10C is eliminated.

A fourth embodiment of a reservoir is illustrated in FIG. 10D. In thisembodiment, the reservoir 90 has an elongated shape, so that it can beinserted in the human body through trocars. The outer shell of thereservoir 94 is rigid. The reservoir is separated into two variablevolume parts 95 and 96 by a piston 97. The piston can slide within thereservoir in a leak-proof manner, as guaranteed by the choice ofmaterial and the quality of surface or by the addition of o-rings 99.The piston is connected to a spring 98, which in turn is connected tothe wall of the reservoir 90. The spring 98 is always in compression,thus transferring via the piston a positive pressure on the fluid in thevariable chamber 95. When said liquid is introduced in the reservoir 90,said variable chamber 95 expands by further compressing the spring 98 toaccommodate the desired volume of liquid.

It will be understood that various modifications and/or improvementsobvious to the person skilled in the art can be made to the embodimentsdescribed hereinabove without departing from the scope of the inventiondefined by the annexed claims.

For example, the principle of pressure differential used in theembodiment represented in FIGS. 2A to 2H can be applied to theembodiment represented in FIGS. 3 to 7 with corresponding results: ahigher pressure at the inlet 46 would accordingly be used to displacethe piston 32 and expel the fluid through the outlet 47. In such anembodiment, the axis 52 could be removed. Such higher pressure can becreated by the use of reservoirs as described above which areelastically compliant and maintain a certain pressure on the liquid theycontain.

In FIGS. 11A to 11D, a specific embodiment of an eccentric axis isrepresented in cut view, said axis corresponding to axis 7 of FIGS. 1Ato 1H or axis 52 of FIGS. 3 to 7. As can be readily understood from thedescription above, and for example from FIG. 1B, in this position of thecylinder all the chambers are closed. However, the cylinder must befurther rotated as shown in FIG. 1C, a rotation that is not possible ifthere is not play between the eccentric axis 7 and the opening of thepiston in which it is received since the liquid can not be compressed.

To overcome this problem, there is the following alternative: eitherusing relative play between the parts (in this case the eccentric axisand the opening of the piston) to avoid blockage of the system ordefining a specific profile for the eccentric axis to avoid displacementof the piston in certain positions of the cylinder, while still rotatingthe cylinder.

The disadvantage of a play is of course the fact that it then rendersthe system less precise as regards the quantity of liquid effectivelydelivered.

Accordingly, it can be interesting to develop another solution, as shownin FIGS. 11A to 11D. This solution is based on the principle used forexample for camshaft, in which the eccentric axis is not purelycylindrical but has a different peripheral shape as explained hereunder.

In FIG. 11A, there is represented an eccentric axis 100 (correspondingto axes 7 or 52), which is received in an opening 101 of the piston.Represented on the axis 100 are three centers of rotation, the center102 being the center of rotation of the cylinder (corresponding to theaxis 5 of FIGS. 1A to 1H for example), and a first offset center ofrotation 103 and a second offset center of rotation 104.

These centers of rotation allow to define different sectors of the axis100 which have the same radius. In FIG. 11B, there are two sectors 105and 106 with a constant radius which are defined around the centre ofrotation 102.

Then in FIG. 11C, there are two further sectors 107, 108 which areadjacent to the sectors 105/106 which have different radius and they aredefined around offset center of rotation 104.

Finally in FIG. 11D, there are two more sectors 109, 110 which haveanother radius and are defined around offset center 103.

Is it understood that the sum of each radius (i.e. of sectors 105/106 or107/108 or 109/110) is equal to the width of the opening 101 of thecylinder.

Of course, it is clear that the position of the different sectors withconstant radius must be disposed appropriately relatively to theposition of the chambers in the cylinder, in order to fulfil their aim.

The pump, in all the embodiments described above, may comprise atelemetry system, such as an RFID or Bluetooth module which would allowthe pump to receive and also send signals and information to an externalcontrol unit. The external control unit may be used to program theimplant function (i.e., drug release rates, time profile of bolusdelivery, etc.) but it can also be used to collect functional data fromthe implant, such as history of doses, battery status, state of the goodfunctioning of the device etc. The telemetry system may be also used todeliver energy to the implant, in a manner similar to othertelemetrically energized implantable devices, for example such as thosedescribed in U.S. Pat. No. 5,820,589.

Further, the pump in all the embodiments described above, can beconnected either physically or wirelessly to a physiological signalsensing system which would provide information as to the state ofcertain physiological variables (i.e. pressure, temperature, electricalactivity, etc.). The signal can then be interpreted by the pump, forexample by its calculating means (containing an appropriate program) andused to decide (based on imbedded decision algorithms) whether or not todeliver a therapeutic dose. One such concrete example would be theconnection of a pump to a system measuring ECG or other brain activitysignals, which then would allow the pump to deliver, when needed (forexample based on predetermined parameters), drugs intracranially.Another example would be the use of the pump in heart failure patientswhere end diastolic pressure or volume is measured and this signal isused by the pump to deliver in the vena cava, systemically or directlyto the heart cavities inotropic or other appropriate drug functionregulating drugs. In a similar fashion, the pump can be coupled to anECG measuring system and use this signals to decide when to delivercardiac rhythm management drugs either in the vena cava or directly inthe heart muscle or heart cavities.

For small animal applications, for intracranial, peripheral or otherhuman applications it is essential that the pump is compact with aminimal weight and volume. One such example is given in FIG. 11. Tofurther reduce weight and volume, it is also possible to removebatteries and to store energy in the implant during drug filling, byelastic deformation of a spring or membrane attached to the reservoir.This energy can be gradually released during emptying of the reservoirand be used accordingly to operate the motor. Energy storage can be alsoachieved by the natural human or animal motion, used a system similar tothe automatic (battery-free) watches.

As can be readily understood from the above description, the system ispreferably implanted through a trocar or similar device. Hence, the size(diameter) should not exceed certain values corresponding to the sizesof such devices. Typically, a maximal cross-sectional diameter would beof about 18 mm, but other sizes can be envisaged depending on theapplication and the location where the device is to be implanted.

REFERENCE NUMBERS

-   1 external body-   2 inlet-   3 outlet-   4 cylinder-   5 cylinder axis-   6 piston-   7 piston axis-   8, 8′ inlet chamber-   9 first temporary chamber-   10 second temporary chamber-   11 seal-   12 seal-   13 inner wall of cylinder 4-   14 inner wall of cylinder 4-   15 inner wall of body 1-   16 external body-   17 inlet-   18 outlet-   19 cylinder-   20 cylinder axis-   21 piston-   22,22′ inlet chamber-   23 first temporary chamber-   24 second temporary chamber-   25 seal-   26 seal-   27 inner wall of cylinder 21-   28 inner wall of cylinder 21-   29 inner wall of body 16-   30 cage-   31 cylinder-   32 piston-   33 first disc-   34 chamber of cylinder-   35 channel-   36 channel-   37 cylinder opening-   38 piston opening-   39 seals of piston-   40 banana-shaped chamber-   41 banana-shaped chamber-   42 opening of disc-   43 opening of disc-   44 central opening-   45 body-   46 inlet-   47 outlet-   48 second disc-   49 opening-   50 opening-   51 first axis-   52 second axis-   53 chamber in front of piston-   54-   55 outer body-   56 batteries-   57 electronic circuit-   58 motor-   59 fluid reservoir-   60 opening-   70 elastic delivery chamber-   71 inlet of chamber 70-   72 outlet of chamber 70-   73 stop valve-   74 deformation-   80 reservoir (1^(st) embodiment)-   81 septum-   82 pump-   83 electrical source-   84 electronic device-   85 antenna-   86 outlet of pump 82-   87 reservoir (2^(nd) embodiment)-   88 pump-   89 feed catheter-   90 inflatable body-   91 ring-   92 septum of ring-   100 eccentrical axis-   101 opening-   102 center of rotation of cylinder-   103 first offset center of rotation-   104 second offset center of rotation-   105 first sector around center 102-   106 second sector around center 102-   107 first sector around center 104-   108 second sector around center 104-   109 first sector around center 103-   110 second sector around center 103

1. An implantable delivery device comprising at least a body, an inlet,an outlet, and actuating means, wherein the actuating means comprise atleast an actuator displacing a piston in a rotating cylinder forming atleast one variable volume chamber, the volume of which is varied byrotation of said cylinder thereby pumping liquid such as a drug from areservoir through said inlet and expelling said pumped liquid from saidvariable volume chamber through at least a first temporary chamber andsaid outlet by variation of said volume, wherein the delivery device isan implantable delivery device, and wherein the actuating means comprisean eccentric system in which the cylinder rotates around a first axisand the piston rotates around a second axis both said axes being coaxialand laterally offset.
 2. The device as claimed in claim 1, wherein saidtemporary chamber is situated between said cylinder and said piston. 3.The device as claimed in claim 1, wherein said temporary chamber is oversaid piston.
 4. The device as claimed in claim 1, wherein the devicecomprises two temporary chambers.
 5. The device as claimed in claim 4,wherein the device comprises a first disk in which said temporarychambers are formed, said disc being attached to said cylinder.
 6. Thedevice as claimed in claim 5, wherein the device comprises a second discwith two openings being connected to said inlet and said outlet, saidfirst disc rotating with respect to said second disc.
 7. The device asclaimed in claim 6, wherein said discs are made of metal, plastic,silicon or ceramics.
 8. The device as claimed in claim 1, wherein thedevice comprises a variable volume chamber at each end of the piston. 9.The device as defined in claim 1, wherein the piston comprises at leastone seal.
 10. The device as claimed in claim 1, wherein said second axisis not cylindrical and has sectors with different radius.
 11. The deviceas claimed in claim 1, wherein the actuator is realized by pressure, insuch a way that the pressure of the liquid in said inlet is higher thanthe pressure of the liquid in said outlet thereby displacing said pistonby this pressure differential.
 12. The device as claimed in claim 1,wherein the actuating means comprise a motor linked to an energy sourceand calculating means.
 13. The device as defined in claim 12, whereinthe motor and/or the energy source and/or the calculating means areinside said device.
 14. The device as defined in claim 13, wherein theenergy source is outside the device, the motor is inside the device andenergy is transmitted telemetrically to the motor.
 15. The device asdefined in claim 12, wherein the motor and/or the energy source and/orthe calculating means are outside said device.
 16. The device as claimedin claim 12, wherein the device is able through its calculating means todecide to deliver a therapeutic dose on the basis of predeterminedparameters delivered by a sensing system.
 17. The device as defined inclaim 16, wherein said parameters are physiological parameters.
 18. Thedevice as defined in claim 16, wherein the delivery by the sensingsystem to the calculating means is made wirelessly or via a physicalconnection.
 19. A delivery chamber for a device as defined in claim 1,wherein the chamber comprises at least an elastically compliant chamber,an inlet catheter and an outlet catheter connected to said chamber. 20.A delivery chamber as defined in claim 19, wherein the outlet cathetercomprises a stop valve.
 21. A delivery chamber as defined in claim 20,wherein the stop valve has the shape of a deformation.
 22. A drugdelivery system that can be implanted through a trocar, wherein thesystem comprises at least a delivery chamber as defined in claim
 19. 23.A reservoir for a device as defined in claim 1, wherein the reservoircooperates with a septum used to fill said reservoir.
 24. A reservoir asdefined in claim 23, wherein the reservoir is elastically compliant. 25.A reservoir as defined in claim 23, wherein said reservoir contains apiston cooperating with a spring, said piston delimiting two variablevolume parts in said reservoir, said spring being in compression inorder to transfer via the piston a positive pressure on the fluidpresent in one of said variable chamber.
 26. A reservoir as defined inclaim 23, wherein the reservoir cooperates with a delivery devicethrough a catheter.
 27. A drug delivery system that can be implantedthrough a trocar, wherein the system comprises at least a reservoir asdefined in claim
 23. 28. A system comprising a device as defined inclaim 1, a delivery chamber, and a reservoir.
 29. A drug delivery systemthat can be implanted through a trocar, wherein the system comprises atleast a device as defined in claim 1.